{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T17:48:08Z","timestamp":1790531288253,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:00:00Z","timestamp":1604361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Horizontal Gaze Palsy with Progressive Scoliosis\u20102 with Impaired Intellectual Development (HGPPS2) is a rare congenital disorder characterized by absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence. We report three new patients with HGPPS2 in a consanguineous Pakistani family, presenting varying degrees of progressive scoliosis, developmental delays, horizontal gaze palsy, agenesis of corpus callosum, and absence of cerebral commissures. Analysis of genotyping data identified shared loss of heterozygosity (LOH) region on chromosomes <jats:italic>5p15.33\u201015.31<\/jats:italic>, <jats:italic>6q11.2\u201012<\/jats:italic>, and <jats:italic>18q21.1\u201021.3<\/jats:italic>. A hypothesis\u2010free, unbiased exome data analysis detected an insertion of nucleotide A (c.2399dupA) in exon 16 of the <jats:italic>DCC<\/jats:italic> gene. The insertion is predicted to cause frameshift p.(Asn800Lysfs*11). Interestingly, <jats:italic>DCC<\/jats:italic> gene is present in the LOH region on chromosome 18. Variant (c.2399dupA) in the <jats:italic>DCC<\/jats:italic> gene is considered as the most probable candidate variant for HGPPS2 based on the presence of <jats:italic>DCC<\/jats:italic> in the LOH region, previously reported role of <jats:italic>DCC<\/jats:italic> in HGPPS2, perfect segregation of candidate variant with the disease, prediction of variant pathogenicity, and absence of variant in variation databases. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients; the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. <jats:italic>DCC<\/jats:italic> encodes a netrin\u20101 receptor protein; its role in the development of the CNS has recently been established. Biallelic <jats:italic>DCC<\/jats:italic> mutations have previously been shown to cause HGPPS2. A novel homozygous variant in patients of the reported family extend the genotypic and phenotypic spectrum of HGPPS2.<\/jats:p>","DOI":"10.1002\/ajmg.a.61952","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T18:09:26Z","timestamp":1604426966000},"page":"355-361","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel homozygous frameshift mutation in the <i>DCC<\/i> gene in a Pakistani family with autosomal recessive horizontal gaze palsy with progressive scoliosis\u20102 with impaired intellectual development"],"prefix":"10.1002","volume":"185","author":[{"given":"Ayesha","family":"Zaka","sequence":"first","affiliation":[{"name":"Genomics Research Lab, Department of Biological Sciences International Islamic University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4211-014X","authenticated-orcid":false,"given":"Shaheen","family":"Shahzad","sequence":"additional","affiliation":[{"name":"Genomics Research Lab, Department of Biological Sciences International Islamic University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi Zahid","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Oral &amp; Maxillofacial Surgery Bahria University Medical and Dental College  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Hashim","sequence":"additional","affiliation":[{"name":"Genomics Research Lab, Department of Biological Sciences International Islamic University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-6825","authenticated-orcid":false,"given":"Sulman","family":"Basit","sequence":"additional","affiliation":[{"name":"Center for Genetics and Inherited Diseases Taibah University  Medina Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-52935-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.22.4797"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-019-00692-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.01.010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.07.028"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.035436"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.19-22-09900.1999"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/386796a0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2294591"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.06.013"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3804"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81336-7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.11.2715"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23361"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.021"},{"key":"e_1_2_9_19_1","volume-title":"Molecular cloning a laboratory manual","author":"Sambrook J.","year":"2001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e3181b59bda"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25418"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2005.06.010"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61952","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T01:22:36Z","timestamp":1692235356000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,3]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1002\/ajmg.a.61952"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61952","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,3]]},"assertion":[{"value":"2020-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}